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PMID: 11069287 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 24 ·2000-11-21 ·Pages 13045-50

Antzutkin ON, Balbach JJ, Leapman RD, Rizzo NW, Reed J, Tycko R

Abstract

Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue beta-amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended beta-sheet structure for Alzheimer's beta-amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the beta-sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils. Here we report solid-state NMR measurements, using a multiple quantum (MQ) (13)C NMR technique, that probe the beta-sheet organization in fibrils formed by the full-length, 40-residue beta-amyloid peptide (Abeta(1-40)). Although an antiparallel beta-sheet organization often is assumed and is invoked in recent structural models for full-length beta-amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length beta-amyloid fibrils and applies MQNMR to a significant problem in structural biology.

MeSH Terms
Alanine Amino Acid Sequence Amyloid beta-Peptides/chemical synthesis,chemistry,ultrastructure Dimerization Humans Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular/methods Peptide Fragments/chemical synthesis,chemistry,ultrastructure Protein Structure, Secondary Quantum Theory
Chemicals
Amyloid beta-Peptides Peptide Fragments amyloid beta-protein (1-40) Alanine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Antzutkin O N
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Balbach J J
Leapman R D
Rizzo N W
Reed J
Tycko R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.230315097
Published
2000-11-21
Pages
13045-50
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC27175
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.230315097 PMC Full Text View journal details
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